Toll-like receptor 9 dependent interferon-α release is impaired in severe asthma but is not associated with exacerbation frequency

Immunobiology. 2015 Jul;220(7):859-64. doi: 10.1016/j.imbio.2015.01.005. Epub 2015 Jan 22.


Patients with asthma and chronic obstructive pulmonary disease (COPD) are susceptible to exacerbations, often caused by microbial pathogens. We hypothesised that intracellular Toll-like receptor (TLR) function in blood mononuclear cells (PBMCs) from these subjects would be impaired and that this impairment is related to exacerbation frequency. PBMCs stimulated with a TLR-9 agonist (but not TLR-3 or 7/8) produced significantly less IFN-α in asthma (26 [3-696]pg/ml) compared to control (943 [164-1651]) and COPD (597 [127-1186]) subjects (p = 0.0019) but this was not related to the number of exacerbations per year in asthma or COPD. In COPD, IFN-α levels were related to KCO (% predicted) in COPD (r = -0.41, p = 0.01). IFN-α was derived from plasmacytoid dendritic cells (pDCs) and their frequency was lower in asthma compared to control subjects (control 0.48% [0.33-0.64] versus asthma 0.29% [0.13-0.34], p = 0.019) whereas pDC function per se was not significantly impaired between groups. The mechanism underlying reduced IFN-α production and the clinical consequences in severe asthma remains to be established.

Keywords: Asthma; COPD; Emphysema; IFN-α; pDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asthma / immunology*
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 9 / immunology*


  • Interferon-alpha
  • TLR9 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9